FFAR2 Membrane Protein Introduction

Introduction of FFAR2

FFAR2, also known as FFA2, G-protein coupled receptor 43 (GPR43) or GPCR43, is a 37 kDa G-protein coupled receptor (GPCR) that has 330 amino acids, encoded by the gene mapping at the chromosome 19q13.12. It is a dual-coupling receptor that is coupled to the pertussis toxin-sensitive, G(i/o)-alpha family of G proteins but also to the Gq family proteins. FFAR2 has been studied to participate in a number of biological activities. It can be activated by short-chain fatty acids (SCFAs) that include acetate, propionate, and butyrate. SCFAs act as a source of energy and also serve as signaling molecules. FFAR2 and other free fatty acid (FFA) receptors are regarded as key constituents of the nutrient sensing mechanism and targeting FFA receptors are assumed to provide novel therapies for the management of metabolic disorders, such as diabetes.

Basic Information of FFAR2
Protein Name Free fatty acid receptor 2
Gene Name FFAR2
Aliases FFA2, FFA2R, GPR43,GPCR43, Free Fatty Acid Activated Receptor 2, Fatty Acid Receptor 2
Organism Homo sapiens (Human)
UniProt ID O15552
Transmembrane Times 7
Length (aa) 330

Function of FFAR2 Membrane Protein

FFAs are not only an essential source of fuel and structural components of biomembranes, but also exhibit a wide range of roles, such as modulation of receptor signaling and regulation of gene expression. FFAs play a vital role in maintaining metabolic homeostasis by activating specific GPCR in pancreatic β cells, immune cells, white adipose tissue, and some other tissues. This receptor is involved in varieties of important cellular processes and biological activities via binding with FFA. It is reported that FFAR2 and other FFA receptors are regarded as key components of the human's nutrient sensing mechanism. And targeting them is assumed to discover novel therapies for the management of diabetes and metabolic disorders. Furthermore, FFAR2 can be activated by a major product of dietary fiber digestion, SCFA, including acetate, propionate, and butyrate, and in charge of modulating intestinal immunity and whole-body energy homeostasis.

Intestinal SCFA receptors FFAR2 and FFAR3, and transporters.Fig.1 Intestinal SCFA receptors FFAR2 and FFAR3, and transporters. (Schilderink, 2013)

Application of FFAR2 Membrane Protein in Literature

  1. Ang Z., et al. FFAR2-FFAR3 receptor heteromerization modulates short-chain fatty acid sensing. FASEB J. 2018, 32(1): 289-303. PubMed ID: 28883043

    The review is aimed to investigate that FFAR2 and FFAR3 interact to form a heteromer in primary human macrophages and monocytes by the proximity ligation assay and during heterologous expression in HEK293 cells by the fluorescence resonance energy transfer and bimolecular fluorescence complementation.

  2. Pan P., et al. Loss of FFAR2 promotes colon cancer by epigenetic dysregulation of inflammation suppressors. Int J Cancer. 2018, 143(4): 886-896. PubMed ID: 29524208

    Free fatty acid receptor 2 (FFAR2, also called GPR43) is activated by SCFAs produced when gut bacteria ferment dietary fiber. Thus, this article results suggested that FFAR2 is an epigenetic tumor suppressor who functions at multiple phases of colon carcinogenesis.

  3. Christiansen C. B., et al. The impact of short chain fatty acids on GLP-1 and PYY secretion from the isolated perfused rat colon. Am J Physiol Gastrointest Liver Physiol. 2018, 315(1): G53-G65. PubMed ID: 29494208

    The paper identified that FFAR2 receptor confirmes low-potent partial agonism of acetate, propionate and butyrate, compared to CFMB, a full agonist. Collectively, SCFAs is likely to increase colonic GLP-1/PYY release, but FFAR2/FFAR3 does not seem to be implicated. In contrast, SCFAs are metabolized and appear to act as a colonocyte energy source.

  4. Bindels L. B., et al. Ffar2 expression regulates leukaemic cell growth in vivo. Br J Cancer. 2017, 117(9): 1336-1340. PubMed ID: 28873082

    The article data indicates the role of Ffar2 in the control of leukaemic cell proliferation in vivo and exhibits a modulation of Ffar2 expression by nutritional tools or pharmacological agents might constitute an attractive approach for therapy to tackle the human leukaemia progression.

  5. Brooks L., et al. Fermentable carbohydrate stimulates FFAR2-dependent colonic PYY cell expansion to increase satietyMol Metab. 2017, 6(1): 48-60. PubMed ID: 28123937

    The report demonstrated that FFAR2 is predominantly implicated in regulating the effect of fermentable carbohydrate on metabolism and does it partly by enhancing PYY cell density and secretion. That highlights the potential to treat obesity by targeting enteroendocrine cell differentiation.

FFAR2 Preparation Options

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  1. Schilderink R, et al. (2013). Dietary inhibitors of histone deacetylases in intestinal immunity and homeostasis. Front Immunol. 4, 226.

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